In response to: PAR-04-023, we are proposing a Bioengineering Research Partnership to design and test an extracorporeal device for the treatment of severe sepsis, based on the principle of hemoadsorption. Our multi- disciplinary team comprises basic science and clinical researchers, bioengineering and biomaterials experts, and experts in complex systems modeling. Our proposal will carefully integrate this diverse group of researchers from both technical and biomedical fields, crossing the boundaries of multiple scientific disciplines and leveraging the capabilities of both industry and academia. Our project is entitled Systems Engineering of a Pheresis Intervention for Sepsis (SEPsIS). Severe sepsis (acute onset organ failure in the setting of infection) is a major health problem that kills nearly 250,000 Americans each year and costs billions of dollars. Available therapies for sepsis, including those recently approved, are suboptimal and new therapies are urgently needed. However, the complexities of the inflammatory response network and the high cost of clinical trials, particularly in the critically ill, renders the traditional drug/device development paradigm obsolete. We have previously developed and tested an extracorporeal blood purification device for treatment in chronic renal disease and have adapted this device for the treatment of acute inflammatory diseases. We have also developed and partially calibrated[unreadable]in both rodents and humans[unreadable]a mathematical model of sepsis. This project proposes to integrate these two achievements and, through an iterative design process, develop a device that can be used to treat severe sepsis. The goal of this proposal is to design an extracorporeal blood purification device for the treatment of severe sepsis. This proposal will bring together investigators from the following departments at the University of Pittsburgh: Bioengineering, Chemical Engineering, Critical Care Medicine, Surgery, Medicine, and Mathematics. We will also call on the expertise of two companies, one specializing in adsorbent polymer technology (MedaSorb Technologies, LLC) and the other in complex systems modeling (Immunetrics, Inc.).